The technique of genome editing is derived from adaptive immunity of microorganisms. It is based on an immune system which functions by storing a fragment of a bacteriophage DNA when infected and, upon subsequent infections, the stored sequence is cut and removed by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9: RNA-guided DNA endonuclease enzyme), a nuclease serving as genetic scissors. This process has been developed into a gene correction technique capable of cutting and fixing a desired region even in a genome if a specific base sequence can be recognized by a guide RNA (gRNA) (Woo J W et al., “DNA-free genome editing in plants with preassembled CRISPR-Cas9 ribonucleoproteins,” Nat. Biotechnol., 33(11), 1162-1164, 2015).
This CRISPR technique has drawn much attention as a method capable of treating fundamental causes of diseases induced due to genetic disorders that previously had been classified as incurable diseases. However, there are still problems to be solved, such as inefficient in vivo delivery of a gene editing system and cutting of non-target genes, known as “off-targeting.” In particular, the use of a gene editing system using a Cas9 plasmid, which was the earliest CRISPR method, had to be inspected for safety reasons such as antibiotic resistance and various immune reactions during in vivo delivery. Recently, an alternate system for producing protein gene scissors (Cas9) and guide RNA in a test tube and delivering the resulting product was utilized, but this system also has problems in terms of efficiency of delivery into cells and safety of the protein and RNA (Ramakrishna S. et al., “Gene disruption by cell-penetrating peptide-mediated delivery of Cas9 protein and guide RNA,” Genome Res., 24(6), 1020-1027, 2014).
Additional references are known in this field of gene editing. For example, see, Korean Published Patent No. 10-2015-0101476 (“Target DNA delivery composition including nucleic acid or Cas protein for encoding guide RNA specific to target DNA and Cas protein and use of same, applicant”) filed by Toolgene Inc. and published on Sep. 3, 2015;
Korean Published Patent No. 10-2015-0101477 (“Target DNA cutting composition including nucleic acid or Cas protein for encoding guide RNA specific to target DNA and Cas protein and use of same”) filed by Toolgene Inc. and published on Sep. 3, 2015; and
Korean Published Patent No. 10-2015-0101478 (“Target DNA cutting composition including nucleic acid or Cas protein for encoding guide RNA specific to target DNA and Cas protein and use of same”) filed by Toolgene Inc., publication date: Sep. 3, 2015).
Type 2 diabetes is a disease in which normal sugar metabolism is not taking place due to a relative increase in insulin resistance caused by various causes although an insulin secreting function remains. In particular, glucagon-like peptide-1 (GLP-1), which is involved in insulin resistance, regulates insulin secretion in the pancreas. It is known that in type 2 diabetes there is an increased expression of dipeptidyl peptidase-4 (DPP4), which is known to decompose GLP-1, which in turn leads to increased insulin resistance. In practice, sitagliptin, a known DPP4 inhibitor, and the like are used as medicines for treating type 2 diabetes. However, when such DPP4 inhibitors are used in a formulation, the effect is temporary. Thus, these medicines must be taken every day, and the use thereof with respect to type 2 diabetes accompanying kidney disorders is limited because of side effects. In addition, various other side effects including allergic reactions caused by the medicine have been reported (Lenski M et al., “Effects of DPP-4 inhibition on cardiac metabolism and function in mice.” J. Mol. Cell Cardiol., 51(6), 906-918, 2011).